In the body of a living creature, i.e., in vivo, many chemical substances such as genes, proteins, lipids, and acids are present. These chemical substances are each present as molecules and affect one another. The mutual influence among molecules is referred to as “molecular interaction”.
Because countless molecules are present in vivo, many molecular interactions naturally occur. A molecular interaction does not occur independently and a sequence of molecular interactions often occurs. For example, “molecule A affects molecule B and as a result, molecule B forms molecule C, i.e., the molecular interactions are linked to one another like a string of beads, starting from molecular A to molecular B and, then, to the molecular C. A group of molecular interactions linked in such a manner is referred to as a “pathway”.
A pathway is useful in understanding biological processes. For example, “molecule C is deformed by a molecular interaction of molecule A and molecule B and as a result, the deformation of the molecule C causes a particular disorder”; “the structure of molecule C is maintained by a molecular interaction of molecule A and molecule B and as a result, normal organ function is continued”.
As described in the above examples, an overview of biological processes, regardless of normal or abnormal function, becomes understandable through pathways of molecular interaction sequences. Therefore, building a pathway is important in biological science related fields such as in medical services and pharmaceutical development. There are a number of pathway building methods.
“Curation” is one method. “Curation” is a method of building a pathway, where a specialist called “curator” reads published literature, extracts portions that describe molecular interactions, and combines the molecular interactions to build the pathway.
Because curation is a method of building a pathway based on a human resource of curators, the amount of published literature to be read relates directly to work load. “PubMed” (see, e.g., Pubmed, available online on Sep. 24, 2007) is a website that discloses a database of published literature.
For reference, “KEGG” (see, e.g., KEGG: Kyoto Encyclopedia of Genes and Genomes, available online on Sep. 24, 2007), “BioCarta” (see, e.g., BioCarta, available online on Sep. 24, 2007), etc., are websites that disclose databases of pathways built by curation.
Data mining and text mining by mechanical processing are other examples of pathway building. “Data mining” is a generic name for knowledge finding approaches involving finding hidden relations and meanings by analyzing a large amount of data using various statistical analysis approaches. In particular, obtaining specific findings and ideas by dividing text data (ordinary, natural sentences) into words, etc., and analyzing the appearance frequencies of the words and correlations therebetween is referred to as “text mining”.
The methods employed for specialized text mining in biotechnology include a method of building a pathway, where mechanical syntax analysis is executed on “molecules” that cause molecular interaction, an “action” that each of the molecules exerts, etc. and that are included in published literature and thereby, interactions are extracted to build a pathway. By combining text mining and data mining, pathways that are meaningful in terms of life sciences, e.g., “a pathway related to colon cancer” may be built by a computer.
“MeSH” (MeSH, available online on Sep. 24, 2007) are biological and medical terms used in biological data mining. MeSH stands for Medical Subject Headings and refers to a group of biological and medical terms. MeSH terms are already given to published literature and by calculating the total amount of the MeSH terms, it becomes possible to analyze the significance a particular group of published literature has biologically and medically.
Further, websites disclose a database formed by correlating biological and medical significance to molecules constituting a pathway. OMIM (see, e.g., OMIM, available online on Sep. 24, 2007) and H-invDB (see, e.g., H-inv DB, available online on Sep. 24, 2007) each correspond to such a website. Both databases are formed by correlating genetic significance to the molecules. The biological and medical significance of a molecule, a gene, etc. may be identified by using the data in each of these databases in data mining.
BioCreAtIvE (available online on Sep. 24, 2007) is a reference concerning text mining specialized for biology and pharmaceutical. “BioCreAtIvE” is a research organization. “HPRD” is a website that discloses a database having interaction information preliminarily stored therein (see, e.g., Human Protein Reference Database, available online on Sep. 24, 2007) and “BOND” is a website that provides data for a fee (see, e.g., BOND, available online on Sep. 24, 2007). These websites have registered therein direct interactions between proteins such as “bonding”. Information on the molecular interactions registered therein may be collectively obtained and may be used for data mining, etc.
“ResNet” from ARIADNE GENOMICS, Inc., is a commercial database formed by correlating “types” and “functions” of molecules as the significance of a molecular interaction and the molecules that cause the molecular interaction. Such a database may be purchased and data mining may be executed using the database.
Combining the above text mining with data mining enables a computer to build a pathway significant in terms of life science, such as “pathway associated with colon cancer”. Software having a function of numerically expressing the level of correlation between a medical/biochemical phenomenon, such as a disease, and a pathway built in such a manner is known. MetaCore, a product of US-based GeneGo Inc., is provided as such software (see MetaCore, available online on Sep. 24, 2007). It is not clear, however, whether MetaCore “numerically expresses the level of correlation between a molecular interaction described in a reference and MeSH” or “numerically expresses the level of correlation between a molecule described in a reference and MeSH”.
Further, Japanese Laid-Open Patent Publication No. 2006-146380 introduces a conventional technique of giving “biological and medical” information concerning, for example, a disorder, to a molecular interaction. International Publication Pamphlet No. WO2003-077159 introduces a method of using a set of routes among two or more molecules called “subnet” as an approach of selecting a route that is selected taking into account the degree of relation to a disorder. Subnets each concern a disorder, etc., and are built in advance. When a route is sought, if a subnet concerning a disorder is hit, the selection of a route related to the disorder is enabled.
Japanese Laid-Open Patent Publication No. 2005-122231 discloses a method of displaying a screen to build a network of terms such as compounds concerning a gene, names of disorders, and proteins. This method is an approach where a user designates a term group 1 and a term group 2 to depict, as a network, information from published literature that suggest relations among the terms.
The discovery of a new role of a pharmaceutical leads to an extension of the term of patent right, which is industrially significant. Many pharmaceutical companies around the world are making aggressive efforts to extend the terms of patent rights. The discovery of a new role of a biological molecule such as gene is also academically and industrially beneficial. A method of advancing the discovery of a new role of a molecule, such as a pharmaceutical and gene, functioning in a living body, however, is not particularly found among the above conventional techniques disclosed in each of the cited Nonpatent Literatures and Patent Documents, in the field of pathway analysis.
The conventional technique disclosed in MetaCore, available online on Sep. 24, 2007, goes no further than suggesting a numerical correlation of a pathway brought about by an administered pharmaceutical or a deficient gene and a medical/biological phenomenon, such as “colon cancer”, and does not promote the discovery of a new role played by a molecule, such as an administered pharmaceutical and deficient gene.
Japanese Laid-Open Patent Publication No. 2006-146380 does not offer a technique that promotes the discovery of a new role of an administered pharmaceutical, gene, etc. International Publication Pamphlet No. WO2003-077159 suggests a route of a pathway associated with a disease, but falls short of advancing the discovery of such a route, a new role of a pharmaceutical used in an experiment and a deficient gene.
With contributions to PubMed increasing at steady pace, biological research on biomolecular mechanisms is in constant progress and kept updated. As a result, a pre-built subnet fails to cover some biological/medical information. International Publication Pamphlet No. WO2003-077159, however, presents no alternative and makes no reference to a method of building a computer-based subnet related to diseases and continuously updatable, thus is regarded as insufficient.
Japanese Laid-Open Patent Publication No. 2005-122231 does not present a method of displaying correlations of molecules or inter-molecular links and the biological/medical significance of a chronic idiopathic disease, etc.
Databases giving biological/medical significance to genes, such as OMIM (OMIM, available online on Sep. 24, 2007) and H-invDB (H-inv DB, available online on Sep. 24, 2007), and databases storing interaction information, such as HPRD (Human Protein Reference Database, available online on Sep. 24, 2007) and BOND (BOND, available online on Sep. 24, 2007), are effective as materials for data mining, but have no function of building a pathway. Thus, this makes impossible the study of a biological phenomenon in a pharmaceutical experiment or a deficient gene test enabled by pathways and obviously, does not promote the discovery of a new role of a molecule from the experimental results.
Pathway analysis software, such as MetaCore from US-based GeneGo Inc. (MetaCore, available online on Sep. 24, 2007), offers no function of promoting the discovery of a new role played by a molecule, such as a pharmaceutical and gene, using a pharmaceutical and a deficient gene used in an experiment and a pathway produced as a result of the experiment.
In this manner, the cited Nonpatent Literatures and Patent Documents do not lead to the promotion of discovery of a new role of a pharmaceutical and gene used in an experiment, from a pathway produced as a result of experiment, thus leave an unsolved problem.
The present invention was conceived in view of the above circumstances, and it is therefore an object of the present invention to provide an analysis support program, an analysis support apparatus, and an analysis support method that search for a new role of a molecule to contribute to a reduction in burden on a user, the promotion of new pharmaceutical research/development, and extension of term of patent right.